The Journal of Experimental Medicine
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© The Rockefeller University Press, 0022-1007/1998/10/1359/ $5.00
The Journal of Experimental Medicine, Volume 188, Number 7, October 5, 1998 1359-1368

Articles

Immature Dendritic Cells Phagocytose Apoptotic Cells via {alpha}vβ5 and CD36, and Cross-present Antigens to Cytotoxic T Lymphocytes

Matthew L. Albert*, S.Frieda A. Pearce{ddagger}, Loise M. Francisco*, Birthe Sauter*, Pampa Roy{ddagger}, Roy L. Silverstein{ddagger}, and Nina Bhardwaj*

From the * Laboratory of Cellular Physiology and Immunology, The Rockefeller University, New York 10021; and the {ddagger} Division of Hematology-Oncology, Cornell University Medical College, New York 10021

Dendritic cells, but not macrophages, efficiently phagocytose apoptotic cells and cross-present viral, tumor, and self-antigens to CD8+ T cells. This in vitro pathway corresponds to the in vivo phenomena of cross-priming and cross-tolerance. Here, we demonstrate that phagocytosis of apoptotic cells is restricted to the immature stage of dendritic cell (DC) development, and that this process is accompanied by the expression of a unique profile of receptors, in particular the {alpha}vβ5 integrin and CD36. Upon maturation, these receptors and, in turn, the phagocytic capacity of DCs, are downmodulated. Macrophages engulf apoptotic cells more efficiently than DCs, and although they express many receptors that mediate this uptake, they lack the {alpha}vβ5 integrin. Furthermore, in contrast to DCs, macrophages fail to cross-present antigenic material contained within the engulfed apoptotic cells. Thus, DCs use unique pathways for the phagocytosis, processing, and presentation of antigen derived from apoptotic cells on class I major histocompatibility complex. We suggest that the {alpha}vβ5 integrin plays a critical role in the trafficking of exogenous antigen by immature DCs in this cross-priming pathway.

Key Words: dendritic cells • phagocytosis • CD36 • integrins • cross-presentation

Address correspondence to Nina Bhardwaj, Laboratory of Cellular Physiology and Immunology, The Rockefeller University, 1230 York Ave., New York, NY 10021. Phone: 212-327-7597; Fax: 212-327-8875; E-mail: bhardwn{at}rockvax.rockefeller.edu

Abbreviations used: Ann V, Annexin V; DC, dendritic cell; MCM, monocyte-conditioned medium; PI, propidium iodide; PS, phosphatidylserine.


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